Hepatocellular carcinoma (HCC) represents the predominant form of primary liver cancer and is frequently identified at a late stage, necessitating systemic therapy. However, resistance to first-line tyrosine kinase inhibitor therapies, such as sorafenib and lenvatinib, remains a significant clinical challenge. Recent research has revealed a strong link between aerobic glycolysis and drug resistance in HCC. Key enzymes in the glycolytic pathway, such as hexokinase, phosphofructokinase, and pyruvate kinase M, play central roles in the metabolic reprogramming of HCC cells. Aberrant activation of these enzymes not only promotes swift proliferation of tumor cells but also boosts adaptability. Lactate, the final product of glycolysis, is also pivotal in contributing to drug resistance in HCC. Moreover, signaling pathways, such as AMPK, HIF-1, and c-Myc, play key roles in tumor metabolic regulation, influencing energy balance, gene expression under hypoxia, and metabolic pathway control. These mechanisms interact synergistically, allowing HCC cells to endure and proliferate despite targeted therapies, ultimately resulting in drug resistance. Therefore, a deeper understanding of these metabolic and signaling regulatory mechanisms will help reveal the fundamental causes of drug resistance in HCC and provide new targets and directions for future therapeutic strategies.

Inner primer Blockers inhibit non-specific amplification in LAMP.

Amid the global trend toward smooth implants' use, implant stability has become a progressively significant concern for augmentation mammaplasty. During the dual-plane augmentation via the inframammary fold (IMF) approach, IMF fixation suture-suturing the Scarpa's fascia to the deep fascia-is routinely adopted by surgeons to minimize inferior implant displacement. However, this approach of maintaining implant stability demonstrates inconsistent reliability, particularly with smooth implants. Excluding suboptimal technical factors, the fundamental cause of implant malposition lies in inadequate inferior or lateral support structure. Based on pectoralis major's anatomical foundation and the access characteristics of the IMF incision, the authors introduce an innovative technical refinement-the modified bi-muscular flap (BMF) technique. The procedure involves an L-shaped muscle release that preserves the lateral long-head origins of the muscle, creating an inferior support structure for the implant. A preliminary outcome compared with the dual-plane technique using fixation suture suggests that this new technique may represent a promising alternative for reducing smooth implant malposition and improving long-term stability.

In this study we have discovered the issues of challenges in networking and cyber security, where everything is dependent on the latest technology, and the most significant feature of technology is the network. It is critical to limit the risk of threats to create a stable and reliable network environment for users. According to certain surveys, most security vulnerabilities are caused by "insider risks." That is, the hazards that arise within companies are greater than the threats that arise externally. There are numerous tools and strategies that can be utilized in a network environment to address security issues and challenges. Although security risks and obstacles can be mitigated with the use of these tools and strategies, it is difficult to make a network completely threat-free. The fundamental cause for this is the rapid advancement of technology and the increasing use of it. According to surveys, security concerns are increasing day by day because of rapid technological change and the growing number of devices connected around the world. Attackers are continuously coming up with new ways to get around the security protections built into devices and networks. Several security technologies and strategies could be utilized in a network to address or lessen these security difficulties and obstacles. Some are software tools, while others are physical tools.

The crisis of global capitalism is a multifaceted phenomenon encompassing economic, political, social, ideological, ecological, and military dimensions. In the present era, the world faces an ongoing and intensifying global crisis rooted in the structural contradictions of the capitalist system. Capitalism sustains itself through an endless process of expansion, which inevitably generates recurring crises of overproduction periods when goods are produced in quantities that cannot be sold due to the limited purchasing power of the majority, a dynamic closely linked to the processes of imperialism. The fundamental cause of these crises lies in the basic contradiction of capitalism, the social character of production versus the private appropriation of material wealth. This contradiction drives the general crisis of the world capitalist system. Despite escalating instability, contemporary society remains distant from revolutionary transformation due to the underdevelopment of the subjective and organizational conditions necessary for systemic change. The relevance of this study lies in the increasing global political instability and the intensifying rivalry and confrontation embedded within international economic processes. The current phase of capitalism is marked by structural crises, financial volatility, and systemic inequalities. Moreover, capitalism’s core features such as, private ownership, market-driven economies, profit orientation, global trade networks, industrial revolutions, capitalist-colonial legacies, financial expansion etc. have simultaneously generated economic progress while deepening inequality, exploitation, and ecological degradation. This paper adopts a comprehensive and critical approach to examine contemporary trends and contradictions within global capitalism. It argues that capitalism is not a monolithic system but exists in multiple forms shaped by historical and regional contexts. The analysis highlights the chaotic and unplanned nature of the world economy, characterized by imbalances and disorder stemming from the spontaneous operation of economic laws rooted in private-property-based commodity production. Furthermore, the paper explores how global capitalism has influenced Manipur, particularly through the lens of identity politics, shaping structural inequalities, ethnic divisions, and capitalist-colonial legacies that perpetuate cycles of violence. Similar patterns can be observed in other global contexts such as China–Taiwan, Russia–Ukraine, Israel–Palestine, North Korea–South Korea etc. In this framework, capitalism represents the broader structural perspective, whereas identity politics emerges as a narrower, myopic view within the larger crisis of global capitalism. The Manipur conflict is thus interpreted both as a symptom of this broader crisis and as a manifestation of identity-based politics under global capitalism.

The fundamental causes of disaster vulnerability: Subsistence agricultural land loss in rural Malawi

The micro-newton cusped field Hall thruster is an electric propulsion device that employs microwave-assisted ionization control. It serves as an actuator in drag-free control systems, ensuring control accuracy and stability by providing continuously adjustable thrust over a wide range. However, a mode transition occurring during the regulation process can lead to a sudden change in anode current, degrading control precision and stability. Therefore, it is necessary to investigate the underlying patterns of mode transition. This study examines the variations in internal plasma parameters and discharge characteristics of the thruster before and after microwave mode transition, primarily through probe diagnostics.Experimental results indicate that before the mode transition, the plasma luminous region is primarily concentrated within the electron cyclotron resonance (ECR) area, approximately 1-3 mm upstream of the anode. After the transition, the luminous region moves further upstream, and the plasma density near the anode exceeds the cutoff density, dropping sharply along the axial direction. The fundamental cause of the change in electron heating mechanism is the alteration in the propagation characteristics of fundamental waves due to this plasma density variation.When the plasma density rises to the cutoff density, the R-wave and O-wave, which drive ionization, are rapidly attenuated or reflected. At this point, the R-wave cannot reach the resonance layer, causing the dominant ECR ionization to become ineffective. The ionization mechanism shifts from being dominated by the R-wave and O-wave to being dominated primarily by the O-wave. Consequently, the electron heating mechanism transitions from volume heating to surface wave heating. This research will provide a basis for subsequent optimization of microwave transmission in the thruster and for reducing the threshold at which mode transition occurs.

Crosstalk regulation between gut microbiota and DNA methylation: Sex-specific effects of intestinal metabolic activities induced by prothioconazole and prothioconazole-desthio in zebrafish.

Hospital and obstetric unit closures are concentrated in the rural Southern United States, often where marginalized racial/ethnic groups reside and access to maternal health care is already strained. Given structural racism's role as a fundamental cause of inequities, we hypothesized that closure effects may vary by race and racial composition of county. We used linked North Carolina birth certificates and Medicaid claims from births occurring to rural residents from 2014 to 2019. Using a Trial Emulation Policy Approach with a Difference-in-Difference analysis, we estimated the effects of hospital and obstetric closures on postpartum acute care (maternal emergency department visit or hospital admission) by race and county racial composition. We categorized rural counties as lower (LNHW, <80% White) or higher (HNHW, ≥80% White) Non-Hispanic White. We found declines in postpartum acute care associated with closures: 3.6 percentage points in LNHW counties and 1.8 percentage points in HNHW counties. We also found that marginalized groups experienced the largest declines, for example, Black versus White birthing people in LNHW counties (-7.1vs -2.5 percentage points). As hospitals and obstetric units continue to close, increasing support in the postpartum period will be crucial for maternal health.

Peacekeeping operations in the 21st century have evolved beyond traditional stability mission to encompass more complex objectives, including civilian protection, conflict resolution, and the management of asymmetric threats. In this shifted paradigm, artificial intelligence (AI) and virtual reality (VR) technologies present unique prospects to improve operational effectiveness and safety of peacekeeping personnel. While there is substantial research on military applications of AI, there remains a striking lack of studies exploring the integration of AI within the UN's peacekeeping mission. This study aims to examine how AI and AI-enabled virtual reality (VR) simulations can enhance the preparedness and response of peacekeepers deployed in high-risk areas. This study is qualitative in nature and adopts phenomenological approach. This research explores the experiences of peacekeepers who were deployed in countries such as Democracy Republic of Congo (DRC), South Sudan, and Mali, and Central African Republic (CAR). It also includes perspectives from experts involved in peacekeeping training department. Findings indicate that AI technologies, particularly with respect to surveillance and intelligence gathering, have potential to enhance situational awareness and lessen the risks posed from emerging threats. Furthermore, AI-driven virtual reality (VR) training simulation creates opportunities for peacekeepers to exercise and enhance their skill of interacting with the community and assist in decision making. Nonetheless, the study also highlights challenges and concerns, including ethical consideration, potential violations of core peacekeeping principles and limitations in the resources required to build AI-based infrastructure. The research demonstrates the potential of AI and VR to transform and modernize peacekeeping, but stressed the need for responsible implementation, recognizing the fundamental cause of peace and stability.

Global demographic shifts, marked by below-replacement fertility rates in numerous nations, are significantly influencing economies and cultures, especially in countries like Italy, Japan, and Germany. This study examines the circumstances in Japan, where the fertility rate reached a historic low of 1.20 in 2023, resulting in immediate implications for the demographic composition and workforce. This study examines the fundamental causes of this trend, emphasising work culture, the correlation between marriage and fertility, and current initiatives aimed at addressing demographic and socioeconomic issues.

This research discusses disputes in the 2024 General Election process involving Ummat Party, the General Election Commission of Republic of Indonesia (KPU), and Election Supervisory Agency of Republic of Indonesia (Bawaslu RI). This research also examines the dynamics of the conflict between the General Election Commission of Republic of Indonesia (KPU) and Ummat Party because of Decree of KPU number 528 of 2022 and the inconsistency of data and information. Ummat Party’s dissatisfaction led to fraud in its membership across two provinces. Tensions escalated as Ummat Party openly rejected the decision, only to end when it was declared eligible to contest the 2024 General Election. According to the research results, there was a miscommunication during the selection of political parties, and the dispute intensified due to fraud allegations. Therefore, to understand the reasons and effects of the administration of the 2024 General Election, the dynamics of this disagreement were analysed. This study finds that the fundamental causes of the dispute are data discrepancies, miscommunication, and a perceived lack of transparency during the factual verification. Nevertheless, the General Election Commission of the Republic of Indonesia (KPU) demonstrated its dedication to transparency and objectivity, adhering to electoral principles and existing regulations. This case highlights the vital significance of data accuracy and effective communication in preserving the integrity and public confidence in electoral processes. This qualitative research used interviews and documentation. The data analyses were performed using Conflict Theory, particularly the application of conflict wheel indicators. The informants were representatives of the General Election Commission of Republic of Indonesia (KPU) and the Election Supervisory Agency of the Republic of Indonesia (Bawaslu RI). At the same time, Ummat Party refused to be interviewed.

In the past, dating violence was considered a lover's quarrel between lovers. However, recently, dating violence has expanded beyond simple assault to include violent crimes like rape and murder, raising concerns about it as a serious social issue. In order to eradicate dating violence, revisions to related laws and police response measures are being discussed. Various studies are also being conducted in academia to identify the fundamental cause of social violence. As a result of the analysis of previous studies, social violence is explained as the cause of domestic violence. Therefore, this study attempted to investigate the relationship between domestic violence and social violence. In addition, this study tried to empirically analyze how relationship addiction affects the relationship between domestic violence and dating violence among the main explanatory factors of dating violence. As a result of a survey of 398 college students, it was found that domestic violence affects dating violence. In other words, the higher the experience of domestic violence, the higher the likelihood of experiencing social violence. Furthermore, relationship addiction was found to be statistically significant in the relationship between domestic violence and relationship violence. In other words, higher levels of relationship addiction were associated with a higher likelihood of experiencing relationship violence. Therefore, consistent with numerous previous studies, domestic violence was identified as an explanatory factor for relationship violence, and domestic violence was found to influence both relationship violence and relationship addiction.

This study aims to evaluate and improve the effectiveness of the granulator machine at the NPK Phonska I Plant of PT Petrokimia Gresik through an integrated Overall Equipment Effectiveness (OEE) and Fault Tree Analysis (FTA) approach. The granulator machine frequently fails to achieve the 2024 production target of 37,500 tons per month due to high downtime (89.24 hours/month) and defective products reaching 17,847 tons annually. The research applies OEE to calculate availability, performance efficiency, and quality rate, followed by Six Big Losses classification and FTA to determine the fundamental causes of machine underperformance. The findings show that the average OEE is 62.1%, significantly below the world-class benchmark of 85%, with the largest losses coming from equipment failure (49.00%) and reduced speed losses (37.75%). The novelty of this research lies in the integration of OEE–FTA with additional correlation analysis between downtime and defect ratios and the identification of heat-related and material-variability effects specific to fertilizer granulation. Scientifically, this study contributes a structured improvement framework tailored for the national fertilizer industry, offering evidence-based maintenance strategies and operational insights to support the company’s effort in achieving world-class machine effectiveness.

Global human rights governance is confronted with multiple challenges such as political polarization, economic sanctions, and trust crises, and the deficit problem is not optimistic. Existing theories mostly attribute the predicament of global human rights governance to resource scarcity and uneven distribution, further deducing that human rights standards vary with national conditions. However, the resources required to promote the realization of human rights through governance are not merely an issue of resource development, but also involve how resource endowments can facilitate the maximum realization of human rights through various rights chains. Amartya Sens exchange entitlement theory holds that the fundamental causes of poverty and famine lie in the lack and imbalance of exchange entitlements. By extension, the deep implication and underlying logic of the global human rights governance deficit is the "exchange entitlement deficit," which is specifically manifested in the imbalance of exchange mechanisms for political rights and interests, economic resources, and social opportunities, as well as the insufficient supply of international human rights system public goods in terms of "transparency guarantees" and "protective security." To address the deficit dilemma in global human rights governance, we should improve the exchange entitlement mechanism for human rights in the international arena, ensure that citizens' political rights and economic, social, and cultural rights are protected by institutions, reduce the transaction costs and information costs for people to realize their human rights, and truly establish the belief in human rights in the international community.

As critical tools in combating global weed resistance, the environmental fate of 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibiting herbicides is a subject of significant concern. This study utilizes the novel herbicide benzobicyclon (BZB) and its hydrolysates (BH, BOH) as a model system, employing an experimentally validated density functional theory (DFT) framework to uncover the structural origins of their environmental behavior at the atomic and electronic levels. Our calculations reveal that BZB's exceptional photostability originates from its higher electronic excitation energy (Eex = 4.15 eV) and a delocalized lowest unoccupied molecular orbital (LUMO), which together create energetic and spatial barriers against photodegradation. In contrast, its metabolites BH (3.85 eV) and BOH (3.72 eV) are less stable due to lower excitation energies and LUMOs localized on degradable functional groups. Furthermore, by calculating the Gibbs free energy of solvation (ΔGsolv), we quantitatively reproduced the experimentally observed solubility trend (BOH > BH > BZB), confirming that polar groups introduced via hydrolysis are the fundamental cause of their enhanced aqueous mobility. More importantly, this work introduces a novel hypothesis linking chiroptical properties to biological activity: BZB's predicted strong electronic circular dichroism (ECD) signal is a spectral fingerprint of its unique, 'preorganized' three-dimensional conformation, which is optimized for stereoselective fitting within the HPPD target enzyme's active site. In summary, this research not only elucidates the environmental behavior mechanisms of BZB and its metabolites but also provides a computational framework that can be used to predict and guide the rational design of the next generation of environmentally safer herbicides.

Research on racism as a fundamental cause of adverse health requires further theoretical guidance. The current article proposes a novel approach to address racial ethnic health disparities that incorporates theories of racism. Racism trauma health theory (RTHT) centers racism as a primary factor in health disparities among African Americans. It analyzes racism as a dynamic and multi-stage process and accounts for levels and domains of racism, types of exposure, specific racist treatment, and stress responses. RTHT addresses limitations of current explanations of racism predicting adverse health by exploring impact beyond economics, to include social, physical, legal, and emotional pathways. The multiplicative effect, at the core of RTHT, assesses compounded experiences of racism that intersect across levels and domains affecting health.

The primary strata of western Taiwan are Cenozoic sedimentary rocks. Characterized by low cementation and high porosity, these rocks exhibit a pronounced wetting–softening effect. Long-term exposure to warm, humid tropical and subtropical climates significantly degrades their engineering geological properties due to weathering. This study, based on a sandstone-shale interbedded highway slope in central Taiwan that has repeatedly collapsed, investigated the slope’s failure mechanism using remote-sensing image interpretation of previous landslides, surface geological surveys, kinematic analysis, photogrammetric mapping, laboratory artificial weathering experiments, and Distinct Element Method (DEM) simulations. The study revealed that the fundamental cause of collapse on this type of oblique-slope interbedded sandstone-shale is the sliding and toppling of sandstone blocks, driven by weathering and erosion of the shale. Based on artificial weathering experiments, the strength loss rate of the shale in the Kuantaoshan Sandstone Member of the Kueichulin Formation after weathering is 6.6 times that of the sandstone. The estimated collapse area from the two-dimensional Distinct Element Method analysis is consistent with the actual value from the photogrammetric model. This type of landslide caused by rock weathering always forms stepped surface where sandstone overhangs above shale. A shale erosion amount of 0.78–0.91 of the spacing of the joint approximately parallel to the slope surface was found to be the critical erosion before collapse and can serve as the early warning indicator.

The construction industry has increasingly embraced lean construction methodologies to improve productivity, minimize waste, and enhance stakeholder value. Despite this growing trend, several challenges hinder the successful adoption of Lean Principles in developing countries. Within the Kurdistan Region of Iraq, the implementation of lean construction remains constrained by multiple barriers that have not been systematically examined. In this study, the challenges associated with lean construction adoption are explored through the application of Root Cause Analysis (RCA) techniques, including fishbone diagrams, Pareto charts, and the "5 Whys" method. RCA provides a structured and analytical approach for identifying the fundamental causes of systemic issues and determining their relative significance. The identified challenges are classified into five main categories: organizational, cultural and human attitudes, technical, governmental and regulatory, and financial. A total of forty-one challenges were recorded, among which twenty-eight were recognized as key obstacles to lean implementation. Moreover, an innovative methodological approach is introduced by focusing on the underlying causes rather than superficial manifestations of lean construction barriers in developing contexts. The findings offer valuable insights for policymakers, project managers, and industry stakeholders, enabling the formulation of targeted strategies that address systemic obstacles, promote organizational transformation, and establish a conducive environment for the effective implementation of lean practices.

Abstract Halide perovskite nanocrystals are highly attractive luminescent materials for next-generation displays due to their outstanding properties, including high photoluminescence quantum yield, excellent color purity, tunable emission wavelengths, and cost-effective solution processability. Their exceptional color purity enables full coverage of the ultra-wide color gamut required for vivid visual experiences in modern display technologies. Light-emitting diodes based on perovskite nanocrystal films have demonstrated external quantum efficiencies exceeding 25%. However, significant performance degradation arises during the pixelation process, a critical step in fabricating high-resolution display devices. Here, we review recent progress and ongoing challenges in advancing perovskite nanocrystal light-emitting diodes for high-resolution applications. We highlight state-of-the-art patterning techniques, stability enhancement strategies, and fundamental causes of efficiency loss, together with progress in integrating devices with thin-film transistor circuits for active-matrix displays. Finally, we discuss future perspectives and key challenges for advancing perovskite nanocrystal light-emitting diodes towards next-generation high-resolution display technologies.